The synthesis and evaluation of several novel antisense DNA analogs are proposed. Antisense oligodeoxynucleotides 15 to 20 nucleotides in length have been shown previously by other workers to inhibit tumor cell growth and viral growth. Design features of the proposed DNA analogs include: (1) the elimination of the metal ion that normally neutralizes the phosphate charge to promote entry into cells, and (2) the placement of a bulky group on the nucleotides to confer resistance to nucleases. Several modified oligodeoxynucleotides will be synthesized. Their following properties will be determined: 1) ability to hybridize with complementary, natural oligonucleotides as monitored by changes in ultraviolet absorbance with changes in temperature, 2) ability to resist nucleases in vitro, and 3) ability to inhibit human immunodeficiency virus in vivo.